Patterns, Predictive Factors, and Prognostic Impact of Contralateral Lateral Lymph Node Metastasis in N1b Papillary Thyroid Carcinoma.

BACKGROUND: Although the incidence among patients with bilateral lateral lymph node metastasis (LLNM) in N1b papillary thyroid carcinoma (PTC) is reported to be as high as 40%, only a few reports have addressed the characteristics of contralateral LLNM. Therefore, this study aimed to investigate the characteristics of patients with contralateral LLNM in N1b PTC. METHODS: This study retrospectively reviewed 834 patients with N1b PTC who underwent modified radical neck dissection between January 1997 and June 2015. RESULTS: Of the 834 N1b PTC patients, unilateral LLNM was found in 728 patients (87.3%) and bilateral LLNM in 106 patients (12.7%). The independent predictors of contralateral LLNM in N1b PTC patients were male sex (adjusted odds ratio [OR], 1.647; p = 0.039), tumor larger than 4 cm (adjusted OR, 6.700; p < 0.001), multiplicity (adjusted OR, 1.754; p = 0.040), bilobar involvement (adjusted OR, 1.971; p = 0.010), and bilateral central LN metastasis (CLNM) (adjusted OR, 2.829; p = 0.025). Moreover, contralateral LLNM significantly increased the risk of overall (adjusted hazard ratio [HR], 1.943; p = 0.016) and lateral neck (adjusted HR, 2.246; p = 0.015) locoregional recurrence. CONCLUSIONS: In the preoperative period, the meticulous evaluation of contralateral lateral neck may be required for male N1b PTC patients with tumor larger than 4 cm, multiplicity, bilobar involvement, and/or bilateral CLNM. In the postoperative period, N1b PTC patients may be re-stratified according to the contralateral LLNM, and meticulous follow-up assessment is required for N1b PTC patients with contralateral LLNM.

Predictive Factors of Lymph Node Metastasis in Follicular Variant of Papillary Thyroid Carcinoma.

BACKGROUND: Compared with conventional papillary thyroid carcinoma (PTC), follicular variant of PTC (FV-PTC) shows less aggressive behavior and better prognosis. Nonetheless, regional lymph node (LN) metastasis was found in 22.8% of FV-PTC patients. Because LN metastasis is a proven predictor of recurrence in PTC, it is important to assess LN metastasis in FV-PTC patients. METHODS: We retrospectively reviewed 134 FV-PTC patients who underwent thyroidectomy with neck dissection. RESULTS: Central LN metastasis (CLNM) and lateral LN metastasis (LLNM) were found in 50 (37.3%) and 16 (11.9%) patients, respectively. In the multivariate analysis for CLNM, male sex (adjusted OR 4.735, p = 0.001), nonencapsulated form (adjusted OR 2.863, p = 0.022), and tumor size >1.0 cm (adjusted OR 3.157, p = 0.008) were independent predictors of high prevalence of CLNM in FV-PTC patients. In the multivariate analysis for LLNM, microscopic extrathyroidal extension (ETE) (adjusted OR 3.939, p = 0.041) and CLNM (adjusted OR 13.340, p = 0.001) were independent predictors of high prevalence of LLNM in FV-PTC patients. CONCLUSIONS: Meticulous perioperative evaluation and prophylactic central neck dissection may be beneficial for FV-PTC patients with male sex, nonencapsulated form, and tumor size >1.0 cm. Moreover, cautious perioperative evaluation of lateral neck LN may be mandatory for FV-PTC patients with microscopic ETE and CLNM.

Computed Tomography-Detected Central Lymph Node Metastasis in Ultrasonography Node-Negative Papillary Thyroid Carcinoma: Is It Really Significant?

BACKGROUND: Because of the limitations in ultrasonography (US), the advantages of computed tomography (CT) for detecting central lymph node (LN) metastasis have been suggested in papillary thyroid carcinoma (PTC). METHODS: First, we compared the diagnostic accuracy of US and CT for detecting central LN metastasis in 6577 central neck levels from 3668 PTC patients. Second, to examine the clinical impact of CT-detected central LN metastasis (CT cN1a) in PTC patients with clinically node negative in US (US cN0), we selected two groups: group I comprised 1245 US cN0 PTC patients who did not have CT scans and did not undergo central neck dissection (CND), while group II comprised 348 US cN0 and CT cN1a PTC patients who underwent CND. After propensity score matching, 254 matched pairs were yielded. RESULTS: For detecting central LN metastasis, CT showed significantly higher sensitivity (38.9 vs. 27.5 %; p < 0.001) and accuracy (66.1 vs. 63.2 %; p < 0.001) than US. Furthermore, US + CT showed significantly higher sensitivity (47.8 vs. 27.5 %; p < 0.001) and accuracy (69.0 vs. 63.2 %; p < 0.001) than US. After matching, radioactive iodine ablation (81.5 vs. 85.8 %; p = 0.235) and locoregional recurrence (p = 0.663) were not significantly different between groups I and II. CONCLUSIONS: Despite the diagnostic advantages of preoperative CT, 'CT-based CND' in US cN0 PTC patients did not significantly influence postoperative management and locoregional recurrence. The strategy for the management of central neck in PTC patients can be sufficiently determined by US only.

Nomogram for predicting central node metastasis in papillary thyroid carcinoma.

BACKGROUND: There was a difficulty for detecting Central lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients. Therefore, the purpose of this study was to design a nomogram for predicting CLNM. METHODS: A total of 10,763 PTC patients who underwent total thyroidectomy with central neck dissection (CND) in Samsung Medical Center were randomly assigned to the training set (n = 7,535) and to the internal validation set (n = 3,228). And, a total of 2,514 PTC patients who underwent total thyroidectomy with CND at Seoul National University Hospital were assigned to the external validation set. RESULTS: The values of the area under the receiver operating characteristic curve in the training set, internal validation set, and external validation set were 0.721 (95% confidence interval [CI], 0.709-0.732), 0.706 (95%CI, 0.688-0.724), and 0.706 (95%CI, 0.685-0.727), respectively. CONCLUSIONS: We recommend the use of our nomogram to enable clinicians and patients to easily personalize and quantify the probability of CLNM during the both pre- and postoperative period. Clinicians may consider the prophylactic CND and meticulous postoperative evaluation in PTC patients with a high nomogram score. J. Surg. Oncol. 2017;115:266-272. © 2016 Wiley Periodicals, Inc.

A novel robotic surgical technique for thyroid surgery: bilateral axillary approach (BAA).

INTRODUCTION: Bilateral axillo-breast approach (BABA) robotic thyroidectomy (RT) is proven to be a feasible method for the treatment of well-differentiated thyroid cancers in terms of oncology as well as cosmesis. However, BABA RT causes postoperative sternal discomfort and needs an incision over the nipple areolar area. Here, we suggest a novel robotic surgical technique for thyroid surgery that does not need a breast incision-bilateral axillary approach (BAA). PATIENTS AND METHODS: We recruited 51 patients who were willing to undergo the novel BAA robotic thyroid surgery. We performed a propensity score-matched analysis to compare the BAA robotic thyroid surgery group (BAA group) with the conventional open thyroid surgery group (open group). RESULTS: Mean operation time in the BAA group (129.7 min) was significantly longer than that in the open group (103.1 min) (p < 0.001). However, no significant differences in the mean number of metastatic lymph nodes (LNs), mean number of retrieved LNs, vocal cord palsy, hypoparathyroidism, and mean stimulated thyroglobulin level were observed between the two groups. There was no case of postoperative bleeding or chyle leak. Of the 51 patients who had undergone the BAA procedure, 27 patients answered the questionnaire. The mean scale, ranging from 0 to 10, at postoperative 1 day/2 weeks was as follows: voice change score, 3.0/1.6; swallowing difficulty score, 4.0/2.0; anterior neck pain score, 4.6/3.6; anterior neck numbness score, 5.4/4.3; right chest pain score, 3.8/2.1; left chest pain score, 3.6/2.3; right chest numbness score, 3.2/2.8; left chest numbness score, 2.4/2.7; right breast pain score, 0.9/0; left breast pain score, 1.2/0; right breast numbness score, 1.7/0; and left breast numbness score, 2.6/0, respectively. CONCLUSION: BAA robotic thyroid surgery is a novel, safe, and feasible oncoplastic method, especially for patients who have fear of procedures around the nipple areolar complex.

Propensity score-matched analysis of robotic versus endoscopic bilateral axillo-breast approach (BABA) thyroidectomy in papillary thyroid carcinoma.

PURPOSE: The da Vinci surgical robot system was developed to overcome the weaknesses of endoscopic surgery. However, whether robotic surgery is superior to endoscopic surgery remains uncertain. Therefore, the purpose of this study was to compare the surgical and oncologic outcomes between endoscopic and robotic thyroidectomy using bilateral axillo-breast approach (BABA). METHODS: Between January 2008 and June 2015, papillary thyroid carcinoma patients who underwent thyroidectomy with central neck dissection using endoscopic (n = 480) or robotic (n = 705) BABA were primarily reviewed. We performed 1:1 propensity score matching and 289 matched pairs were yielded. RESULTS: Operation time was significantly longer in the robotic thyroidectomy than in the endoscopic thyroidectomy (184.9 vs. 128.9 min, P < 0.001). A significantly higher number of central lymph nodes (CLNs) were resected in the robotic thyroidectomy than in the endoscopic thyroidectomy (5.3 vs. 4.4, P = 0.003). However, the incidence of other outcomes including hospital stay, postoperative duration, thyroglobulin level, radioactive iodine ablation, hemorrhage, chyle leakage, wound infection, recurrent laryngeal nerve injury, and loco-regional recurrence did not significantly differ between the endoscopic thyroidectomy and the robotic thyroidectomy. CONCLUSIONS: Endoscopic thyroidectomy is comparable with robotic thyroidectomy in view of surgical complications and LRR. Because robotic thyroidectomy resected a larger number of CLNs than did endoscopic thyroidectomy, further long-term follow-up studies will be required to clarify the possible prognostic benefits of robotic thyroidectomy.

Routine Level 2b Dissection may be Recommended Only in N1b Papillary Thyroid Carcinoma with Three- or Four-Level Lateral Lymph Node Metastasis.

BACKGROUND: Due to the low incidence of level 2b metastasis and the risk of spinal accessory nerve injury, previous studies have argued against routine level 2b dissection for N1b papillary thyroid carcinoma (PTC). However, other studies have suggested the importance of including level 2b during lateral neck dissection. Therefore, this study aimed to determine the necessity of routine level 2b dissection. METHODS: The study retrospectively reviewed 327 N1b PTC patients who underwent unilateral modified radical neck dissection between January 1997 and May 2016. RESULTS: The incidence of level 2b metastasis was 10.4 %, compared with 53.5 % for level 2a metastasis. The univariate analysis showed that large tumor size (p = 0.027) and simultaneous lateral lymph node metastasis (LLNM) (p = 0.002) were significantly associated with level 2b metastasis. The multivariate analysis showed that three-level (adjusted odds ratio [OR] 6.032; p = 0.020) and four-level (adjusted OR 9.398; p = 0.012) simultaneous LLNM were independent predictors for level 2b metastasis. CONCLUSIONS: Due to the low incidence of level 2b metastasis, routine level 2b dissection may not be necessary for N1b PTC patients. Level 2b dissection may be reserved for patients with more than three-level simultaneous LLNM or clinical/radiological evidence of level 2b metastasis.

Predictive Factors for Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

BACKGROUND: Because lymph node (LN) metastasis has been proven to be a predictor for locoregional recurrence (LRR) in papillary thyroid microcarcinoma (PTMC), better knowledge about the predictors for LN metastasis in PTMC is required. METHODS: We retrospectively reviewed 5656 PTMC patients who underwent total thyroidectomy and central neck dissection and/or lateral neck dissection between January 1997 and June 2015. RESULTS: Male gender (adjusted odds ratio [OR] 2.332), conventional variant (adjusted OR 4.266), tumor size >0.5 cm (adjusted OR 1.753), multiplicity (adjusted OR 1.168), bilaterality (adjusted OR 1.177), and extrathyroidal extension (ETE) (adjusted OR 1.448) were independent predictors for high prevalence of central LN metastasis (CLNM), whereas per 10-year age increment (adjusted OR 0.760) and chronic lymphocytic thyroiditis (adjusted OR 0.791) were independent predictors for low prevalence of CLNM. In addition, male gender (adjusted OR 1.489), tumor size >0.5 cm (adjusted OR 1.295), multiplicity (adjusted OR 1.801), ETE (adjusted OR 1.659), and CLNM (adjusted OR 4.359) were independent predictors for high prevalence of lateral LN metastasis (LLNM), whereas per 10-year age increment (adjusted OR 0.838) was an independent predictor for low prevalence of LLNM. There was a statistically significant difference in LRR with regard to nodal stage (p < 0.001). CONCLUSIONS: Meticulous perioperative evaluation of LN metastasis is required for PTMC patients with the above predictors.

Does microscopic positive tumor margin in papillary thyroid cancer really matter?

BACKGROUND: The clinical impact of microscopically positive tumor margin in papillary thyroid cancer is not well studied. The aim of this study is to evaluate the clinical importance of a microscopically positive margin for recurrence in papillary thyroid cancer patients and to examine whether recurrence and recurrence-free survival were affected by the location of the positive margin-anterior or posterior. METHODS: We conducted a retrospective cohort study at a single institution. From January 1997 to June 2015,6,293 papillary thyroid cancer patients who underwent total thyroidectomy with or without neck dissection (central and/or lateral) at the Thyroid Cancer Center of Samsung Medical Center (Seoul, South Korea) were included in the analyses. RESULTS: Of the 6,293 papillary thyroid cancer patients, an operative margin was microscopically involved in 313 (5.0%) on final pathologic report. The mean follow-up time was 77.5 months, and locoregional recurrence was observed in 244 (3.9%) patients. The presence of a microscopically positive margin did not increase the risk of locoregional recurrence (adjusted hazard ratio = 1.079, P = .140) after adjustment for other statistically significant factors in the Cox proportional hazard model. In addition, posterior positive margin was not a risk factor for locoregional recurrence as well (adjusted hazard ratio = 1.24, P = .672). In a propensity score-matching analysis, a microscopically positive margin did not increase the risk of locoregional recurrence. CONCLUSION: Microscopic involvement of the operative margin in papillary thyroid cancer patients, whether anteriorly or posteriorly, does not appear be an independent prognostic factor in recurrence-free survival rates.

Angiopoietin-2 exacerbates cardiac hypoxia and inflammation after myocardial infarction.

Emerging evidence indicates that angiopoietin-2 (Angpt2), a well-recognized vascular destabilizing factor, is a biomarker of poor outcome in ischemic heart disease. However, its precise role in postischemic cardiovascular remodeling is poorly understood. Here, we show that Angpt2 plays multifaceted roles in the exacerbation of cardiac hypoxia and inflammation after myocardial ischemia. Angpt2 was highly expressed in endothelial cells at the infarct border zone after myocardial infarction (MI) or ischemia/reperfusion injury in mice. In the acute phase of MI, endothelial-derived Angpt2 antagonized Angpt1/Tie2 signaling, which was greatly involved in pericyte detachment, vascular leakage, increased adhesion molecular expression, degradation of the glycocalyx and extracellular matrix, and enhanced neutrophil infiltration and hypoxia in the infarct border area. In the chronic remodeling phase after MI, endothelial- and macrophage-derived Angpt2 continuously promoted abnormal vascular remodeling and proinflammatory macrophage polarization through integrin α5ß1 signaling, worsening cardiac hypoxia and inflammation. Accordingly, inhibition of Angpt2 either by gene deletion or using an anti-Angpt2 blocking antibody substantially alleviated these pathological findings and ameliorated postischemic cardiovascular remodeling. Blockade of Angpt2 thus has potential as a therapeutic option for ischemic heart failure.

A Novel Gel Pad Laryngeal Ultrasound for Vocal Cord Evaluation.

BACKGROUND: Laryngeal ultrasound (LUS) is a new method for vocal cord evaluation in patients with risk of vocal cord palsy (VCP). However, the previously described LUS reportedly had a high failure rate of vocal cord visualization in male patients. A novel gel pad LUS was devised to overcome the limitations of the previous method. METHODS: A total of 482 (100 male) consecutive LUS and direct laryngoscopy examinations were performed in thyroidectomy and other neck surgery patients. The conventional LUS and gel pad LUS were used for all patients. Findings were independently cross-validated with direct laryngoscopy. RESULTS: The conventional LUS and gel pad LUS methods had a 93.4% and 99.0% visualization rate, respectively, with a sensitivity of 98.0% for both methods, and a specificity of 99.7% and 99.8%, respectively. Among the 482 patients, 51 patients had VCP and 91 patients had diffuse thyroid cartilage calcification interrupting LUS. CONCLUSION: The new gel pad LUS method significantly enhances the visualization of vocal cords in patients who have diffuse thyroid cartilage calcification interrupting LUS and, therefore, the overall efficacy of LUS as a perioperative diagnostic tool for VCP.

Total thyroidectomy versus lobectomy in conventional papillary thyroid microcarcinoma: Analysis of 8,676 patients at a single institution.

BACKGROUND: Because there is a controversy regarding the management of papillary thyroid microcarcinoma, the purpose of this study was to compare lobectomy with total thyroidectomy as a primary operative treatment for papillary thyroid microcarcinoma. Loco-regional recurrence in the contralateral remnant lobe can be managed safely by completion thyroidectomy via the previous scar. However, reoperation for operation bed (thyroidectomy site) or regional lymph node (central or lateral) recurrence generally is associated with morbidity. Therefore, we analyzed overall loco-regional recurrence and loco-regional recurrence outside of the contralateral remnant lobe separately. METHODS: We retrospectively reviewed 8,676 conventional patients with papillary thyroid microcarcinoma who underwent thyroidectomy. RESULTS: Lobectomy was performed in 3,289 (37.9%) patients, and total thyroidectomy was performed in 5,387 (62.1%) patients. Total thyroidectomy significantly decreased the risk of overall loco-regional recurrence (adjusted hazard ratio 0.398, P < .001). However, total thyroidectomy did not significantly decrease the risk of loco-regional recurrence outside of the contralateral remnant lobe (adjusted hazard ratio 0.880, P = .640). Particularly in conventional papillary thyroid microcarcinoma patients with multifocality, total thyroidectomy significantly decreased the risk of overall loco-regional recurrence (adjusted hazard ratio 0.284, P = .002) and loco-regional recurrence outside of the contralateral remnant lobe (adjusted hazard ratio 0.342, P = .020). CONCLUSION: Although lobectomy is associated with contralateral remnant lobe recurrence, lobectomy did not increase the risk of loco-regional recurrence outside of the contralateral remnant lobe in patients with papillary thyroid microcarcinoma, except in those with multifocality. Because recurrence in the contralateral remnant lobe can be managed safely by completion thyroidectomy, lobectomy may be a safe operative option for select patients with papillary thyroid microcarcinoma without multifocality.

Should Level V Be Routinely Dissected in N1b Papillary Thyroid Carcinoma?

BACKGROUND: For N1b papillary thyroid carcinoma (PTC) patients, modified radical neck dissection (MRND) encompassing levels II-V is generally recommended. However, routine level V dissection is controversial because of the low incidence of metastasis/recurrence in level V and the increased morbidities associated with level V dissection. METHODS: This study retrospectively reviewed 646 N1b PTC patients who underwent unilateral MRND between January 1997 and June 2015. Specifically, to assess surgery-related outcomes of level V dissection, outcomes from N1b PTC patients who underwent unilateral MRND (levels II-V) were compared with those who underwent unilateral selective neck dissection (SND; levels II-IV) using propensity score matching. RESULTS: Overall and occult level V metastases were observed in 13.9% and 8.6% of patients, respectively. Level V recurrences were observed in only 2.26 (7.7%) recurred N1b PTC patients who underwent unilateral MRND. In multivariate analysis, three-level (II, III, and IV) simultaneous metastasis (adjusted odds ratio = 3.079, p = 0.003) was an independent predictor for level V metastasis. Under a matched condition, "shoulder syndrome" encompassing shoulder dysfunction and pain (9.1% vs. 2.7%, p = 0.002) was significantly more frequent in the MRND group than it was in the SND group. CONCLUSIONS: Because of the low incidence of metastasis/recurrence in level V and the clear evidence of increased morbidities, level V dissection in N1b PTC patients may be reserved for those with three-level simultaneous metastasis or clinically/radiologically evident level V metastasis.

Predicting Factors for Bilaterality in Papillary Thyroid Carcinoma with Tumor Size <4 cm.

BACKGROUND: In the 2015 American Thyroid Association guidelines, either lobectomy or total thyroidectomy was recommended for thyroid cancer <4 cm without extrathyroidal extension (ETE) and lymph node (LN) metastasis. Therefore, the purpose of this study was to investigate factors predictive of bilaterality in papillary thyroid carcinoma (PTC) patients with tumor size <4 cm. METHODS: This study retrospectively reviewed 3296 conventional PTC patients who underwent total thyroidectomy with central neck dissection and/or lateral neck dissection between January 2008 and June 2015. RESULTS: In overall conventional PTC patients, per 10-year age increment (adjusted odds ratio [OR] = 1.153, p < 0.001), BRAF mutation positivity (adjusted OR = 1.447, p = 0.002) and multifocality (adjusted OR = 3.895, p < 0.001) were independent predictors for bilaterality. In conventional PTC patients with tumor size 1-4 cm, per 10-year age increment (adjusted OR = 1.289, p < 0.001), BRAF mutation positivity (adjusted OR = 1.560, p = 0.012), multifocality (adjusted OR = 4.220, p < 0.001), and N1b (adjusted OR = 1.570, p = 0.007) were independent predictors for bilaterality. In conventional PTC patients with tumor size <1 cm, BRAF mutation positivity (adjusted OR = 1.327, p = 0.042) and multifocality (adjusted OR = 3.530, p < 0.001) were found to be independent predictors for bilaterality. CONCLUSIONS: When multifocality and BRAF mutation positivity are observed in PTC patients with tumor size <4 cm, total thyroidectomy may be considered. If lobectomy is performed in PTC patients with multifocality and BRAF mutation positivity, meticulous follow-up is needed to detect hidden malignancies in the contralateral lobe.

Follicular and Diffuse Sclerosing Variant Papillary Thyroid Carcinomas as Independent Predictive Factors of Loco-Regional Recurrence: A Comparison Study Using Propensity Score Matching.

BACKGROUND: Only about half of papillary thyroid carcinoma (PTC) cases are classified as conventional PTC (CV-PTC), whereas various histologic variants constitute the remaining cases. Since controversies about the clinical behavior and outcomes of PTC variants continue, the purpose of this study was to compare the outcomes of patients with PTC variants who were treated at a large tertiary referral center in Korea. METHODS: The medical records for 15,598 CV-PTCs, 435 follicular variants of PTC (FV-PTCs), and 66 diffuse sclerosing variants of PTC (DSV-PTCs) were retrospectively reviewed. Loco-regional recurrences (LRR) among PTC variants were compared using propensity score matching. RESULTS: Analysis I compared CV-PTC with FV-PTC. After rigorous matching, 367 pairs were established. Recurrence-free survival (RFS) rates in CV-PTC were 96.1% at 5 years, 92.2% at 10 years, and 92.2% at 15 years, while those for FV-PTC were 98.8% at 5 years, 98.8% at 10 years, and 98.8% at 15 years (p = 0.026). Analysis II compared CV-PTC with DSV-PTC. Rigorous matching yielded 56 pairs. RFS rates for CV-PTC were 87.4% at 5 years, 87.4% at 10 years, and 87.4% at 15 years, while those for DSV-PTC were 68.9% at 5 years, 57.5% at 10 years, and were not available at 15 years (p = 0.013). CONCLUSIONS: Compared with CV-PTC, FV-PTC showed less aggressive behaviors and more favorable outcomes. However, DSV-PTC showed more aggressive behaviors and a less favorable outcome than CV-PTC did. Therefore, the management strategy and follow-up plan for PTC should be differentiated according to the histologic variant.

Chronic lymphocytic thyroiditis and BRAF V600E in papillary thyroid carcinoma.

It has been reported that papillary thyroid carcinoma (PTC) with chronic lymphocytic thyroiditis (CLT) is less associated with extrathyroidal extension (ETE), advanced tumor stage and lymph node (LN) metastasis. Other studies have suggested that concurrent CLT could antagonize PTC progression, even in BRAF-positive patients. Since the clinical significance of the BRAF mutation has been particularly associated with conventional PTC, the purpose of this study was to determine the clinical significance of CLT according to BRAF mutation status in conventional PTC patients. We retrospectively reviewed the medical records of 3332 conventional PTC patients who underwent total thyroidectomy with bilateral central neck dissection at the Thyroid Cancer Center of Samsung Medical Center between January 2008 and June 2015. In this study, the prevalence of BRAF mutation was significantly less frequent in conventional PTC patients with CLT (76.9% vs 86.6%). CLT was an independent predictor for low prevalence of ETE in both BRAF-negative (OR=0.662, P=0.023) and BRAF-positive (OR=0.817, P=0.027) conventional PTC patients. In addition, CLT was an independent predictor for low prevalence of CLNM in both BRAF-negative (OR=0.675, P=0.044) and BRAF-positive (OR=0.817, P=0.030) conventional PTC patients. In conclusion, BRAF mutation was significantly less frequent in conventional PTC patients with CLT. However, CLT was an independent predictor for less aggressiveness in conventional PTC patients regardless of BRAF mutation status.

BRAF V600E mutation: Differential impact on central lymph node metastasis by tumor size in papillary thyroid carcinoma.

BACKGROUND: The necessity of prophylactic central neck dissection is one of debating issues in the treatment of papillary thyroid carcinoma (PTC). In a previous study, the predictive value of BRAF mutation for lymph node metastasis was only significant in 0.5 to 1.0 cm PTC. Thus, we assess the predictive value of BRAF mutation for central lymph node metastasis according to tumor size. METHODS: Medical records of 3107 patients with PTC who underwent thyroidectomy with central neck dissection were retrospectively reviewed. RESULTS: BRAF mutation was a predictor for central lymph node metastasis in 2.0 to 4.0 cm PTC (odds ratio [OR] = 3.494; p = .002). Although BRAF mutation was associated with central lymph node metastasis in 0.5 to 1.0 cm PTC in univariate analysis (OR = 1.334; p = .047), this significance was not observed in multivariate analysis (OR = 1.232; p = .163). BRAF mutation was not associated with central lymph node metastasis in other tumor sizes. CONCLUSION: Prophylactic central neck dissection could be considered in 2.0 to 4.0 cm PTC with positive BRAF mutation. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1203-E1209, 2016.

Radioactive iodine ablation may not decrease the risk of recurrence in intermediate-risk papillary thyroid carcinoma.

The use of radioactive iodine (RAI) ablation in patients with intermediate-risk papillary thyroid carcinoma (PTC) who show microscopic extrathyroidal extension (ETE), regional lymph node (LN) metastasis, tumors with aggressive histology, or vascular invasion has been debated due to the lack of data regarding long-term prognosis in this risk group. Therefore, the purpose of this study was to resolve the controversy surrounding the prognostic benefit of RAI ablation, especially in intermediate-risk PTC patients. We retrospectively reviewed the medical records of 8297 intermediate-risk PTC patients who underwent primary total thyroidectomy with or without neck dissection at the Thyroid Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, between January 1997 and June 2015. Of these 8297 patients, 7483 (90.2%) received RAI ablation. After adjusting for clinicopathological characteristics, RAI ablation did not significantly decrease the risk of loco-regional recurrence (LRR) (adjusted hazard ratio (HR) 0.852, P 0.413). Moreover, RAI ablation did not decrease the risk of LRR even in intermediate-risk PTC patients with aggressive features such as BRAF positivity (adjusted HR 0.729, P 0.137), tumor size >1 cm (adjusted HR 0.762, P 0.228), multifocality (adjusted HR 1.032, P 0.926), ETE (adjusted HR 0.870, P 0.541), and regional LN metastasis (adjusted HR 0.804, P 0.349). Furthermore, high-dose RAI ablation (>100 mCi) did not significantly decrease the risk of LRR (adjusted HR 0.942, P 0.843). Therefore, RAI ablation in intermediate-risk PTC patients should be considered on the basis of tailored risk restratification.

Prophylactic Central Neck Dissection Might Not Be Necessary in Papillary Thyroid Carcinoma: Analysis of 11,569 Cases from a Single Institution.

BACKGROUND: The benefits of prophylactic central neck dissection (pCND) remain controversial in clinically node-negative (cN0) papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the clinical impact of pCND with a large group of cN0 PTC patients. STUDY DESIGN: A total of 11,569 cN0 PTC patients who underwent thyroidectomy between January 1997 and June 2015 were investigated. Using Cox multivariate analysis, the prognostic impact of pCND was assessed using subset analyses according to various clinicopathologic conditions. Using propensity score matching, various surgical morbidities were assessed under adjusted conditions. RESULTS: Of 11,569 cN0 PTC patients, 8,735 (75.5%) underwent pCND. Prophylactic CND did not significantly decrease the risk of locoregional recurrence in cN0 PTC patients (adjusted hazard ratio [HR] = 0.874; p = 0.392). In addition, pCND did not significantly decrease the risk of locoregional recurrence in various surgical extents (lobectomy and ipsilateral pCND [adjusted HR = 0.636; p = 0.131], total thyroidectomy and ipsilateral pCND [adjusted HR = 0.775; p = 0.164], and total thyroidectomy and bilateral pCND [adjusted HR = 1.041; p = 0.821]). However, surgical morbidities, such as temporary vocal cord palsy (5.6% vs 2.5%; p = 0.001), temporary hypoparathyroidism (30.8% vs 16.7%; p < 0.001), and permanent hypoparathyroidism (3.5% vs 1.7%; p < 0.001) were significantly more frequent in the pCND(+) group. CONCLUSIONS: Given the lack of proven benefits and the clear evidence of morbidities, pCND cannot be recommended as a routine procedure. We suggest that CND be reserved for therapeutic situations.

Influence of Body Mass Index and Body Surface Area on the Behavior of Papillary Thyroid Carcinoma.

BACKGROUND: Previous studies have examined the relationship between body mass index (BMI) and the behavior of papillary thyroid carcinomas (PTC). However, the results are inconsistent. The purpose of this study was to clarify the association between PTC behavior and anthropometric parameters including BMI and body surface area (BSA). METHODS: This study retrospectively reviewed 5081 PTC patients who underwent total thyroidectomy with bilateral central neck dissection between January 2002 and June 2015. Because of sexual dimorphism in obesity, analyses were conducted separately for men and women. The World Health Organization BMI classification was used to classify patients as normal (18.5 ≤ BMI <25 kg/m(2)), overweight (25 ≤ BMI <30 kg/m(2)), or obese (BMI ≥30 kg/m(2)). Since no consensus for BSA categorization exists, enrolled patients were grouped into BSA quartiles by sex: women BSA1 (BSA <1.52 m(2)), BSA2 (1.52 ≤ BSA <1.59 m(2)), BSA3 (1.59 ≤ BSA <1.67 m(2)), and BSA4 (BSA ≥1.67 m(2)); and men BSA1 (BSA <1.77 m(2)), BSA2 (1.77 ≤ BSA <1.86 m(2)), BSA3 (1.86 ≤ BSA <1.96 m(2)), and BSA4 (BSA ≥1.96 m(2)). RESULTS: In women, overweight (adjusted odds ratio [OR] = 1.187, p = 0.042) and obese (adjusted OR = 2.231, p < 0.001) were independent predictors for multiplicity. Furthermore, overweight (adjusted OR = 1.237, p = 0.012) and obese (adjusted OR = 1.789, p = 0.005) were independent predictors for extrathyroidal extension (ETE). However, higher BMI was not an independent predictor for bilaterality or central lymph node metastasis (CLNM). In addition, higher BSA-BSA3 (adjusted OR = 1.205, p = 0.049) and BSA4 (adjusted OR = 1.524, p < 0.001)-was an independent predictor for multiplicity. However, higher BSA was not a predictor for bilaterality, ETE, or CLNM. In men, higher BMI and BSA were not predictors for multiplicity, bilaterality, ETE, or CLNM. CONCLUSIONS: In women with PTC, higher BMI was an independent predictor for multiplicity and ETE. Furthermore, higher BSA was an independent predictor for multiplicity. However, BMI and BSA were not predictors for the PTC behavior in men.